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SOGC joint clinical practice guideline

No. 284, December 2012

Colposcopic Management of Abnormal


Cervical Cytology and Histology
Abstract
This clinical practice guideline has been prepared
by the Executive Council of the Society of Canadian Objective: To provide a guideline for managing abnormal cytology
Colposcopists and approved by the Society of Obstetricians results after screening for cervical cancer, to clarify the appropriate
and Gynaecologists of Canada/Society of Gynecologic algorithms for follow-up after treatment, and to promote the best
Oncology of Canada/Society of Canadian Colposcopists possible care for women while ensuring efficient use of available
Policy and Practice Guidelines Committee, the Executive resources.
and Council of the Society of Gynecologic Oncology of
Outcomes: Women with abnormal cytology are at risk of developing
Canada and the Executive and Council of the Society of
cervical cancer; appropriate triage and treatment will reduce
Obstetricians and Gynaecologists of Canada.
this risk. This guideline will facilitate implementation of common
PRINCIPAL AUTHOR standards across Canada, moving away from the current trend of
James Bentley, MB ChB, Halifax NS individual guidelines in each province and territory.

THE EXECUTIVE COUNCIL OF THE Evidence: Published literature was retrieved through searches of
SOCIETY OF CANADIAN COLPOSCOPISTS PubMed or Medline, CINAHL, and The Cochrane Library in October
2008 using appropriate controlled vocabulary (e.g., colposcopy,
James Bentley, MB ChB, Halifax NS cervical dysplasia) and key words (e.g., colposcopy management,
Monique Bertrand, MD, London ON CIN, AGC, cervical dysplasia, LEEP, LLETZ, HPV testing, cervical
dysplasia triage). Results were restricted to systematic reviews,
Lizabeth Brydon, MD, Regina SK
randomized control trials/controlled clinical trials, and observational
Hlne Gagn, MD, Ottawa ON studies. There were no date or language restrictions. Searches were
Brian Hauck, MD, Calgary AB updated on a regular basis and incorporated in the guideline to July
2012. Grey (unpublished) literature was identified through searching
Marie-Hlne Mayrand, MD, Montreal QC the websites of health technology assessment and health technology
Susan McFaul, MD, Ottawa ON assessment-related agencies, clinical practice guideline collections,
and national and international medical specialty societies.
Patti Power, MD, St. Johns NL
Expert opinion from published peer-reviewed literature and
Alexandra Schepansky, MD, Edmonton AB
evidence from clinical trials is summarized. Consensus opinion is
Marina Straszak-Suri, MD, Ottawa ON outlined when evidence is insufficient.
SPECIAL CONTRIBUTORS Values: The quality of the evidence is rated using the criteria described
Terry Colgan, MD, Toronto ON by the Canadian Task Force on Preventive Health
Care (Table 1).
Laurette Geldenhuys, MD, Halifax NS
Validation: This guideline has been reviewed for accuracy from content
Mark Heywood, MD, Vancouver BC
experts in cytology, pathology, and cervical screening programs.
Roberta Howlett, PhD, St. Thomas ON Guideline content was also compared with similar documents from
Linda Kapusta, MD, Mississauga ON other organizations including the American Society for Colposcopy and
Cervical Pathology, the British Society for Colposcopy and Cervical
Rachel Kupets, MD, Toronto ON Pathology, and the European Cancer Network.
Joan Murphy, MD, Toronto ON
Jill Nation, MD, Calgary AB
J Obstet Gynaecol Can 2012;34(12):11881202
Vyta Senikas, MD, Ottawa ON
Michael Shier, MD, Toronto ON
Key Words: Cervical cytology, cervical cancer, colposcopy,
Disclosure statements have been received from all authors. treatment, follow-up, abnormalities, guidelines

This document reflects emerging clinical and scientific advances on the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.

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Colposcopic Management of Abnormal Cervical Cytology and Histology

Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task Force
on Preventive Health Care
Quality of evidence assessment* Classification of recommendations
I: Evidence obtained from at least one properly randomized A. There is good evidence to recommend the clinical preventive action
controlled trial
II-1: Evidence from well-designed controlled trials without B. There is fair evidence to recommend the clinical preventive action
randomization
II-2: Evidence from well-designed cohort (prospective or C. The existing evidence is conflicting and does not allow to make a
retrospective) or casecontrol studies, preferably from recommendation for or against use of the clinical preventive action;
more than one centre or research group however, other factors may influence decision-making
II-3: Evidence obtained from comparisons between times or D. There is fair evidence to recommend against the clinical preventive action
places with or without the intervention. Dramatic results in
uncontrolled experiments (such as the results of treatment with E. There is good evidence to recommend against the clinical preventive
penicillin in the 1940s) could also be included in this category action

III: Opinions of respected authorities, based on clinical experience, L. There is insufficient evidence (in quantity or quality) to make
descriptive studies, or reports of expert committees a recommendation; however, other factors may influence
decision-making
*The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Force on
Preventive Health Care.95
Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the Canadian Task Force
on Preventive Health Care.95

Recommendations 02. At colposcopy, 2 or more biopsy specimens should be


taken. (I-A)
Managing Cytological Abnormalities
03. An endocervical curettage should be performed when the
The age of the patient may affect management and where pertinent transformation zone is not visible in women with an AGC
will be identified in the recommendation. Pap smear and in women over 45 years old with high-grade
cytology. (II-2B)
The Colposcopy Examination
04. Routine HR-HPV testing for all colposcopy referrals is
01. Colposcopic findings are best described according to the discouraged. (III-C)
terminology defined by the International Federation for Cervical
Pathology and Colposcopy. (III-C) Managing Women With ASCUS or LSIL
on Referral for Colposcopy
05. A woman with persistent ASCUS/LSIL or ASCUS HR-HPV
ABBREVIATIONS positive cytology should be referred for colposcopy as directed
AC adenocarcinoma by provincial/territorial guidelines. (III-A)

AGC-N atypical glandular cells-favour neoplasia 06. A colposcopically identified lesion should be biopsied. (III-C)
AGC-NOS atypical glandular cells-not otherwise specified 07. If no lesion is identified, biopsies of the transformation zone
AGUS atypical glandular cells of undetermined significance should be considered. (III-C)
AIS Adenocarcinoma in situ
Managing ASC-H
ALTS ASCUS/LSIL Triage Study for Cervical Cancer
08. A woman with an ASC-H Pap smear should have colposcopy to
ASC-H atypical squamous cells-cannot exclude
rule out CIN 2 or 3 and/or cancer. (II-2A)
high-grade squamous intraepithelial lesion
ASCUS atypical squamous cells of undetermined 09. Biopsies should be performed on any identifiable lesions at
significance colposcopy. (II-2A)
CIN cervical intraepithelial neoplasia 10. With an ASC- H Pap smear, the finding of negative colposcopy
ECC endocervical curettage does not automatically warrant a diagnostic excisional
procedure. (III-E)
HPV human papillomavirus
HR-HPV high-risk HPV Managing HSIL
HSIL high-grade squamous intraepithelial lesion 11. All women with an HSIL test result should have
LEEP/ LLETZ loop electrosurgical excision procedure/large loop colposcopy. (II-2A)
excision of the transformation zone
12. In the absence of an identifiable lesion at colposcopy, whether
LSIL low-grade squamous intraepithelial lesion satisfactory or unsatisfactory, an endocervical curettage and
Pap smear Papanicolaou smear directed biopsies should be performed. (III-B)
SCC squamous cell carcinoma 13. In women with HSIL, when the transformation zone is not seen
TZ transformation zone in its entirety and endocervical curettage and/or biopsy results

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are negative, a diagnostic excisional procedure should be Managing CIN 2 or 3 in Women


considered. (III-B) Aged 25 Years and Over
29. CIN 2 or 3 should be treated. Excisional procedures are
Managing Atypical Glandular Cytology preferred for CIN 3. (II-1A)
(AGC-NOS, AGC-N, AIS)
30. Women who have positive margins should have follow-up with
14. The finding of an AGC Pap smear warrants colposcopy. (II-2A) colposcopy and directed biopsies and/or endocervical curettage.
15. All women with an AGC Pap smear should have an endocervical Treatment for recurrent or persistent CIN 2 or 3 should be by
curettage. Women over 35 years of age or with a history of excision. (II-1B)
abnormal bleeding should have endometrial sampling. (II-2A)
Managing CIN 2 or 3 in Women Less Than 25 Years Old
16. Women with an AGC-N Pap smear without an identifiable
lesion at colposcopy should undergo a diagnostic excisional 31. The pathologist should be asked to clarify whether the lesion is
procedure. (II-2A) CIN 2 or CIN 3. (III-B)
32. CIN 2 in women less than 25 years old should be
Managing Squamous Cell Carcinoma and observed with colposcopy at 6-month intervals for up to
Adenocarcinoma on Cytology 24 months before treatment is considered. (II-2B)
17. Women with a cytologic diagnosis suggestive of carcinoma, 33. CIN 3 in women less than 25 years old should be
with or without a visible lesion, should have colposcopy and treated. (III-B)
appropriate biopsies. (III-A)
Managing Adenocarcinoma in Situ
Managing the Patient With Abnormal HPV
34. If AIS is diagnosed, treatment needs to be a diagnostic
Test and Normal Cytology
excisional procedure, or type 3 transformation zone
18. Women less than 30 years old should not have HR-HPV testing excision. (II-2A)
done as a screen with cytology. (II-2E)
35. If margins are positive after diagnostic excisional procedure,
19. Women less than 30 years old who are HR-HPV positive and a second excisional procedure should be performed. (II-2A)
have normal cytology should be followed as per provincial/
36. If after treatment for AIS a woman has finished childbearing,
territorial guidelines; colposcopy is not required. (III-B)
a hysterectomy should be considered. (III-B)
20. Women 30 years old and over who test positive for HR-HPV
37. If AIS is diagnosed after LEEP is performed for CIN in a woman
and have negative cytology should have HR-HPV and cytology
who has not completed her family and margins are negative,
testing repeated at 12 months. Persistent positive HR-HPV tests
it is unnecessary to perform a further diagnostic excisional
warrant colposcopy. (I-A)
procedure. (II-2E)
Managing Abnormal Cytology in Pregnancy
Managing Histological Abnormalities During Pregnancy
21. Women with an ASC-US or LSIL test result during pregnancy should
38. If CIN 2 or CIN 3 is suspected or diagnosed during pregnancy,
have repeat cytology testing at 3 months post pregnancy. (III-B)
repeat colposcopy and treatment should be delayed until 8 to 12
22. Pregnant women with HSIL, ASC-H, or AGC should be referred weeks after delivery. (II-2A)
for colposcopy within 4 weeks. (III-B)
23. Endocervical curettage should not be performed during Follow-up Post Treatment for CIN 2 or 3
pregnancy. (III-D) Either option is acceptable:
39. Women should be followed with cytology testing and colposcopy
Managing Abnormal Cytology in at 6-month intervals for 2 visits. If both cytology and any biopsies
Women Less Than 21 Years Old are negative, they will then return to screening per provincial/
territorial guidelines. (II-2B)
24. Cytological screening should not be initiated in women less than
21 years old. (II-2E) 40. HPV testing at 6 months combined with cytology testing is
acceptable. If both are negative, women may return to screening
25. If screening is done in a woman less than 21 years old, and an
per provincial/territorial guidelines. (II-2B)
ASC-US or LSIL result is reported, cytology should be repeated
only per provincial or territorial guidelines. (III-B)
Managing Histological Abnormalities in Women at High Risk
26. A woman less than 21 years old who has cytology results of
41. Immunocompromised women do not require screening
ASC-H, HSIL, and AGC should be referred for colposcopy. (III-B)
colposcopy. (II-2D)
Managing Histological Abnormalities
Wait Times for Colposcopy
Managing CIN 1
42. Women with ASC-H or AGC should be seen in a colposcopy
27. The preferred option for biopsy-proven CIN 1 is observation clinic within 6 weeks of referral. (III-C)
with repeat assessment at 12 months with cytology testing.
43. Women with HSIL should ideally be seen in a colposcopy
(Colposcopy at 12 months is an acceptable option.)
clinic within 4 weeks of referral. (III-C)
Management should be according to the cytology
result. (II-1B) 44. Women with a Pap smear suggestive of carcinoma
should be seen in a colposcopy clinic within 2 weeks of
28. In the case of a patient with biopsy-proven CIN 1 after HSIL
referral. (III-C)
or AGC, cytology and histology should be reviewed, where
available. If a discrepancy remains, then an excisional biopsy 45. All other women with abnormal results should be seen in a
may be considered. (III-B) colposcopy clinic within 12 weeks of referral. (III-C)

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INTRODUCTION THE COLPOSCOPY EXAMINATION

O ver the last 30 years cervical cancer morbidity and


mortality rates have dropped significantly in Canada,
from approximately 30 per 100000 to 7 per 100000
Colposcopy is the examination of the lower genital tract
and cervix using magnification from a colposcope with
a good light source. The squamocolumnar junction and
women.1 This change has been widely attributed to the transformation zone should be identified; this determines
availability of cervical screening via cytologic sampling.2 whether the examination is satisfactory or not. Acetic acid is
then used to assess the size, shape, margin, and location of
Colposcopy has evolved to become a tool for evaluating any neoplastic lesion. These findings can then be described
those with abnormal cytology and obtaining histological according to the new nomenclature of the International
samples by biopsy. Treatment of lesions can then be Federation for Cervical Pathology and Colposcopy.14
performed, usually preserving fertility and making major
surgery unneccesary.3 Numerous jurisdictions have When any lesion is identified, recent evidence supports
developed guidelines48 for colposcopy, and these have the practice of taking at least 2 biopsy specimens to
been reviewed in developing this document. improve the accuracy of colposcopy. A biopsy should be
performed and specimens taken of the most severe area
Cervical cancer screening is organized within each found on colposcopic examination to confirm or rule out
province and territory in Canada. Screening programs issue malignant lesions.15,16 Analysis of the ALTS data showed
screening and follow-up recommendations for abnormal that taking 2 biopsies for a low-grade cytology referral at
screening results, including referral for colposcopy. The initial colposcopy improved the sensitivity (to detect CIN 2
diversity and status of cervical screening in Canada has or greater) to 81.8%, compared with 68.3% with 1 biopsy.15
been summarized elsewhere.9
A recent review of the utility of endocervical curettage was
A review of the recommended age for initial screening published using data from Calgary. Using data from over
was initiated by the American Society of Colposcopy 13000 examinations, the authors showed that 99 ECC
and Cervical Pathology, which in June 2009 convened a specimens had to be taken to detect 1 additional case of
consensus practice improvement conference that included CIN 2 or higher grade lesion. The largest benefit was in older
representatives from the United States and Canada. women referred after high-grade cytology.17 An ECC should
Outcomes from this meeting included a recommendation thus be performed in the case of unsatisfactory colposcopy,
to start screening at age 21.10 This recommendation has an AGC smear, and in older women with high-grade cytology.
been incorporated into new guidelines from Quebec,11 A low threshold is recommended for undertaking a biopsy.
Alberta,12 and Ontario.13 If any lesion is seen, biopsy should be completed. If only
Canadian colposcopic practice is unique in several ways. metaplasia is in question, a biopsy should be considered.
Colposcopy is performed predominantly by gynaecologists Unless dictated by the appropriate algorithm, there is no
in both hospital clinics and private offices. Access to HPV role for routine HR-HPV testing in the colposcopy clinic.
testing is currently limited outside teaching hospitals.
Clinical Tip: HPV Vaccination
The primary aim of these guidelines is to standardize the
A womans visit to the colposcopy clinic is an opportune time
colposcopic care provided for women in Canada. to discuss HPV vaccination with her. Even if she has not been
previously vaccinated a woman may benefit from vaccination to
prevent new HPV infections.
COLPOSCOPIC MANAGEMENT OF
CYTOLOGICAL ABNORMALITIES
Recommendations
Screening and colposcopy recommendations vary across 1. Colposcopic findings are best described
provinces and territories and have been documented according to the terminology defined by the
elsewhere.9 Current guidelines for colposcopic referrals International Federation for Cervical Pathology
can be summarized as follows: referral for colposcopy is and Colposcopy. (III-C)
recommended for persistent ASCUS, persistent or incident 2. At colposcopy, 2 or more biopsy specimens should
LSIL, ASC-H, HSIL, and AGC, as well as for Pap smears be taken. (I-A)
that suggest squamous or glandular carcinoma. HPV 3. An endocervical curettage should be performed
testing is not widely available; however, when reflex HPV when the transformation zone is not visible in
testing shows the presence of oncogenic or HR-HPV with women with an AGC Pap smear and in women
ASCUS cytology, referral for colposcopy is recommended. over 45 years old with high-grade cytology. (II-2B)

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4. Routine HR-HPV testing for all colposcopy MANAGING ASC-H


referrals is discouraged. (III-C) With an ASC-H result on the Pap smear, significant
pathology is typically found in the majority of cases.
MANAGING WOMEN WITH ASCUS OR LSIL In a study of 517 cases from Edmonton, Alberta, CIN
ON REFERRAL FOR COLPOSCOPY 2 or greater was detected in 70% of cases. Most cases
were CIN 2; however, invasive carcinoma was reported
Management of low-grade abnormalities remains in 2.9% of cases and AIS in 1.7%.24 A similar Ontario
controversial. A large randomized trial in the United States study showed CIN 2 or greater in 59.4% of cases with
concluded that women with LSIL cytology results were a stronger correlation in women under 40 years of age.25
best managed by immediate referral for colposcopy; it was All women with ASC-H should have colposcopy to rule
noted that 83% were positive for HR-HPV and thus HPV out significant pathology. If colposcopy is negative,
triage would not be effective.18 The same study reported recommendations include repeat colposcopy, repeat
that women with ASCUS results, but negative for HR- cytology and, ideally, HR-HPV testing twice, at 6-month
HPV, could safely be triaged away from colposcopy.18 This intervals, to ensure a significant lesion is not missed. If
approach requires access to reflex HPV testing, which these repeat tests are negative, women may return to
unfortunately is not widely available in Canada. A recent regular screening, as per provincial/territorial protocol.
multicentre study in the United Kingdom evaluated the The finding of ASC-H with negative colposcopy does
management of similar low-grade cytology. The study not warrant a cone biopsy or excisional procedure for
concluded that there was no clear benefit of a policy of diagnostic purposes.
immediate colposcopy as although it detects more cervical
intraepithelial neoplasia grade II or more severe disease, Recommendations
it leads to a large number of referrals with no high grade 8. A woman with an ASC-H Pap smear should
cervical intraepithelial neoplasia [and] overtreatment with have colposcopy to rule out CIN 2 or 3 and/or
associated after effects in young women.19 cancer. (II-2A)
9. Biopsies should be performed on any identifiable
With low-grade lesions, colposcopy is done to rule out lesions at colposcopy. (II-2A)
potentially premalignant changes i.e., CIN 2 or 3; if these 10. With an ASC-H Pap smear, the finding of
are detected, management is undertaken according to the negative colposcopy does not automatically
appropriate protocol. A meta-analysis reported CIN 2+ warrant a diagnostic excisional procedure. (III-E)
rates of 10% and CIN 3+ of 6% with an ASCUS referral.20,21
With an LSIL referral, the rates of CIN 2+ are 17% and MANAGING HSIL
CIN 3+ 12%.22,23 If CIN 1 is the highest grade identified
The risk of a significant lesion is high with HSIL cytology.
at colposcopy, conservative management is recommended.
Studies have shown CIN 2 or greater in 53% to 66% of
If no lesion is identified at colposcopy, a random biopsy
cases in which colposcopic biopsies are undertaken, and up
at the transformation zone should be considered. As
to 90% if an immediate LEEP is performed.26,27 Because
per consensus opinion, if no dysplasia is identified at
of this high rate of significant high-grade histology, all
colposcopy, annual screening with the referring health care women with an HSIL result should have colposcopy. A
provider is recommended until 3 negative Pap smears have visual assessment and LEEP approach may be appropriate
been reported. If all cytology is negative, women may then in some circumstances, but a colposcopically directed
be followed every 2 to 3 years, consistent with provincial/ biopsy and tailored treatment is preferred.
territorial guidelines.
If a lesion is not detected at colposcopy and colposcopy
Recommendations
is not satisfactory, then a diagnostic excisional
5. A woman with persistent ASCUS/LSIL or ASCUS procedure should be done. This can be achieved with
HR-HPV positive cytology should be referred for a cone biopsy, or LEEP using a large loop, or a second
colposcopy as directed by provincial/territorial endocervical pass. However, if no lesion was detected
guidelines. (III-A) and colposcopy was satisfactory, combined colposcopy
6. A colposcopically identified lesion should be and cytology is appropriate at 6-month intervals for
biopsied. (III-C) 2 visits. This situation is rare. For women who have
7. If no lesion is identified, biopsies of the finished childbearing, a diagnostic excisional procedure
transformation zone should be considered. (III-C) should be considered.

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Recommendations with colposcopy, cytology testing, ECC, and HR-HPV


testing at 12 months. If a lesion is identified, treatment
11. All women with an HSIL test result should have
is in accordance with the guideline specific to the type
colposcopy. (II-2A)
of lesion. If a carcinoma is identified, referral should
12. In the absence of an identifiable lesion at
be made to a gynaecologic oncologist. If all follow-up
colposcopy, whether satisfactory or unsatisfactory,
is negative after 2 years, routine cytologic testing may be
an endocervical curettage and directed biopsies
should be performed. (III-B) resumed.
13. In women with HSIL, when the transformation Recommendations
zone is not seen in its entirety and endocervical 14. The finding of an AGC Pap smear warrants
curettage and/or biopsy results are negative, colposcopy. (II-2A)
a diagnostic excisional procedure should be 15. All women with an AGC Pap smear should have
considered. (III-B) an endocervical curettage. Women over 35 years of
age or with a history of abnormal bleeding should
MANAGING ATYPICAL GLANDULAR have endometrial sampling. (II-2A)
CYTOLOGY (AGC-NOS, AGC-N, AIS) 16. Women with an AGC-N Pap smear without an
identifiable lesion at colposcopy should undergo a
The finding of AGC-NOS, AGC-N, or AIS always diagnostic excisional procedure. (II-2A)
warrants prompt referral for colposcopy in the absence
of other symptomatology. Neoplastic lesions found
in areas other than the cervix, including endometrium, MANAGING SQUAMOUS CELL CARCINOMA
AND ADENOCARCINOMA ON CYTOLOGY
ovary, and fallopian tube, have been identified with AGC
cytology.2830 In a Canadian report, 456 cases of AGC or Women should be referred promptly for colposcopy if
AGUS were identified from a database of over 1 million their Pap smear is suggestive of carcinoma, with or without
Pap smears (0.043%).29 On final histologic follow-up, 7% a visible lesion. Assessment should include colposcopy
were found to have CIN 1, 36% were found to have CIN and directed biopsy, and ECC should be considered. If no
2 or 3, AIS was identified in 20%, carcinoma of the cervix abnormality is detected, a diagnostic excisional procedure
in 9%, and endometrial pathology in 29%, including is recommended to rule out occult carcinoma. Endometrial
carcinoma of the endometrium in 10%. It should be biopsy should also be contemplated in the workup of
noted that CIN is consistently the most frequent finding women with adenocarcinoma found by Pap smear.
across many studies.28-31 This high rate of pathology
precludes any attempt to triage using repeat cytology or Recommendation
HPV testing. 17. Women with a cytologic diagnosis suggestive of
carcinoma, with or without a visible lesion, should
The diagnosis of AGC-N is associated with higher rates of have colposcopy and appropriate biopsies. (III-A)
abnormalities and thus, in the absence of an abnormality
found by colposcopy, a diagnostic excisional procedure
MANAGING THE PATIENT WITH ABNORMAL
should be performed.32,33 These procedures includes cold HPV TEST AND NORMAL CYTOLOGY
knife cone biopsy and laser cone biopsy and may include
LEEP if the specimen is of sufficient size. A hysterectomy Women with ASCUS and positive reflex HR-HPV should
is not considered a diagnostic excisional procedure. be referred for colposcopy. However, no provincial
Endocervical curettage should be done in all women, and guidelines address management of negative cytology
endometrial sampling should be performed in women findings combined with a positive HR-HPV result.
who are over 35 years or who have a history of abnormal
bleeding, including anovulation. Women with negative cytology and positive HPV results
should have both tests repeated with their primary health
However, with AGC-NOS cytology and the absence of care provider after 12 months.34,35 If both tests are negative
an identified lesion, women are still at risk of developing at 12 months, women should return to being screened
a lesion. In this situation, follow-up assessment every according to provincial/territorial guidelines. Women with
6 months for 2 years includes repeat cytology testing, a cytological abnormality should be managed according to
colposcopy, and ECC. If HR-HPV testing is available the cytological diagnosis. If there is persistent HR-HPV on
and was done at the initial colposcopy visit, women who 2 tests 1 year apart, referral for colposcopy is recommended
test negative for HR-HPV may have repeat assessment to rule out the possibility of a high-grade lesion.

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Recommendations HPV infection and low-grade abnormalities found by


Pap smears are common in this age group, most of these
18. Women less than 30 years old should not have HR-
infections and related cytological changes will resolve
HPV testing done as a screen with cytology. (II-2E)
without intervention.39,40 Screening is invasive and can
19. Women less than 30 years old who are HR-HPV
have adverse psychological sequelae, especially if it leads
positive and have normal cytology should be
to colposcopy referral.10,41
followed as per provincial/territorial guidelines;
colposcopy is not required. (III-B) If this screening leads to treatment by LEEP, this can later
20. Women 30 years old and over who test positive be associated with a slightly increased risk of premature
for HR-HPV and have negative cytology should rupture of membranes and preterm delivery.42,43 HPV
have HR-HPV and cytology testing repeated at 12 vaccination has recently been instituted in Canada, and the
months. Persistent positive HR-HPV tests warrant high efficacy against HPV 16 and 18 should result in fewer
colposcopy. (I-A) high-grade lesions needing treatment.44-48 The American
Congress of Obstetricians and Gynecologists and several
MANAGING ABNORMAL Canadian organizations have therefore recommended that
CYTOLOGY IN PREGNANCY screening begin at 21 years of age.1113,4952
The indications for colposcopy in pregnant women are In women less than 21 years, if a Pap smear has been done
essentially the same as in non-pregnant women. If a low- and abnormalities are detected at screening, management
grade lesion (ASCUS or LSIL) is found during pregnancy, should be conservative to prevent harm. Low-grade
the Pap smear should be repeated 3 months postpartum. changes, i.e., ASC-US and LSIL, regress in up to 93%
This practice is safe as the rate of cancer in this group is of cases with conservative management. Thus women
very low.36 If HSIL, ASC-H, or AGC is found, prompt less than 21 years with ASC-US and LSIL results should
evaluation with colposcopy is essential. If colposcopy is have cytology testing repeated in 1 year, with referral to
unsatisfactory in the first trimester, it should be repeated colposcopy only if abnormalities persist for 24 months.10
after 20 weeks gestation when, because of the physiological Women less than 21 years with ASC-H, HSIL, or AGC
changes, the cervix everts itself and the squamocolumnar results should be referred for colposcopy.
junction may become visible.
Recommendations
If CIN 3 or carcinoma is suspected, biopsy is recommended. 24. Cytological screening should not be initiated in
There is evidence that biopsy in pregnancy is not harmful.37 women less than 21 years old. (II-2E)
Women with high-grade dysplasia in pregnancy should be 25. If screening is done in a woman less than 21 years
seen by an experienced colposcopist. old, and an ASC-US or LSIL result is reported,
cytology should be repeated only per provincial or
Recommendations territorial guidelines. (III-B)
21. Women with an ASC-US or LSIL test result during 26. A woman less than 21 years old who has cytology
pregnancy should have repeat cytology testing at results of ASC-H, HSIL, and AGC should be
3 months post pregnancy. (III-B) referred for colposcopy. (III-B)
22. Pregnant women with HSIL, ASC-H, or
AGC should be referred for colposcopy within MANAGING HISTOLOGICAL ABNORMALITIES
4 weeks. (III-B)
23. Endocervical curettage should not be performed Once a lesion has been identified on colposcopy and
during pregnancy. (III-D) biopsy has been completed, a decision must be made
regarding management. The aim of treatment is to
MANAGING ABNORMAL CYTOLOGY IN THE remove a potentially precancerous lesion to prevent
WOMAN LESS THAN 21 YEARS OLD development of carcinoma. The initial classification of
There is little evidence that screening by cytology testing in cervical intraepithelial neoplasia as CIN 1, 2, or 3 was
adolescents (<21 years old) is beneficial. The incidence of proposed by Richart in 1973 and reinforced by the World
cervical cancer is very low. The Surveillance, Epidemiology, Health Organization in 1994.53 The natural history of
and End Results data from the United States showed dysplastic lesions has been more fully elucidated in
a rate of 0.1/100000 in women 15 to 19 years old and recent years, and this has led pathologists to adopt a
1.6/100000 in women 20 to 24 years old, compared with 2-tiered cytologic terminology to describe histological
15.5/100000 in women 40 to 45 years old.38 Although lesions. A recent consensus project led by the College

1194 l DECEMBER JOGC DCEMBRE 2012


Colposcopic Management of Abnormal Cervical Cytology and Histology

Table 2. Evolution of cervical cancer precursors53


Progression
Regression, Persistence, Progression to towards invasive
CIN grade % % CIN 3, % cancer, %
CIN 1 57 32 11 1
CIN 2 43 35 22 5
CIN 3 32 < 56 not known > 12

of American Pathologists and the American Society for must be no suspicion of glandular disease; there is no
Colposcopy and Cervical Pathology recommended the cytological/histological disparity; and the patient has not
following terminology for HPV-associated squamous had previous treatment.
lesions: Low-grade squamous intraepithelial lesion
and high-grade squamous intraepithelial lesion, which Cryotherapy is not recommended for treatment of CIN 3.55
may be further classified using the CIN terminology.51
If excision with LEEP is used the size of loop electrode
This guideline uses the CIN terminology. The rate
must be adjusted depending on the lesion: a type 2 TZ
of progression of these dysplastic lesions has been
requires a larger loop electrode than a type 1 TZ to
well reviewed by Ostor52 (Table 2), and over time the
ensure the lesion is fully excised. If the lesion is not seen
therapeutic approach has been adapted to prevent harm
in its entirety, colposcopy is unsatisfactory and ablative
when lesser CIN grades are unlikely to progress to
therapies should not be used.17,56 Care should be taken to
invasive cancer.
avoid removal of excessive cervical stroma, which would
Treatment modalities include excisional and ablative predispose women to preterm delivery, especially if very
approaches (cryotherapy or laser ablation). The favoured large loops are used or multiple passes taken.
method in Canada is excisional, the loop electrosurgical
excision procedure, which is relatively easy to perform as an A type 3 TZ with a lesion that extends into the
outpatient procedure, although there can be complications. endocervical canal or a glandular lesion requires a larger or
A recent meta-analysis estimated that after a LEEP longer excision for adequate evaluation or treatment. This
procedure the risk for preterm delivery in a subsequent document adopted the new the International Federation
pregnancy of less than 32 to 34 weeks gestation, was 1 in of Cervical Pathology and Colposcopy terminology to
143 treatments.42 The same research group suggested that identify this procedure as a type 3 excision to avoid the
a depth threshold of 10 mm is also a variable in reducing current confusion in terminology.17 Currently, cone biopsy,
harm. Consequently, if the colposcopist is able to adjust diagnostic excisional procedure, laser excision and LEEP
the procedure to the lesion, negative sequelae in future may be used but have different meanings to individual
pregnancy may be minimized.54 colposcopists.56

Treatment is tailored to the lesion identified on the cervix Managing CIN 1


by either removal or ablation of the entire transformation Evidence from the recent ALTS trial has confirmed
zone. The International Federation of Cervical Pathology significant interobserver variability in the histological
and Colposcopy has classified the transformation zone into diagnosis of CIN 1, with the overlap often observed with
three categories.17 A type 1 TZ is completely ectocervical benign HPV infection.57 Our current understanding is that
and fully visible. A type 2 TZ is fully visible, has an CIN 1 seldom progresses to invasive disease and that it
endocervical component, and may have an ectocervical will regress without treatment within 2 to 5 years in 60%
component. A type 3 TZ is predominantly endocervical, to 80% of all cases.54,57 Regression rates are even more
not fully visible, and may have an ectocervical component pronounced in adolescents, with regression of low-grade
(Figure). squamous intra-epithelial lesions in up to 91% of cases
over a 3-year period.56 This knowledge has led to a change
Using this classification, ablative methods can be used for in the treatment philosophy for CIN 1.
a type 1 or 2 TZ if the following criteria are met: the TZ
must be fully visible; a colposcopically directed diagnostic Conservative management with observation is preferred
biopsy must be taken from the most dysplastic area in the for CIN 1. Women should be followed with repeat cytology
TZ; there must be no suspicion of invasive disease; there testing at 12 months, which can be done by the primary

DECEMBER JOGC DCEMBRE 2012 l 1195


SOGC joint clinical practice guideline

Transformation zone categories

Type I Type II Type III

completely ectocervical has an endocervical has an endocervical


component component

fully visible fully visible not fully visible

small or large may have ectocervical may have ectocervical


ectocervical component component, which may component, which may
be small or large be small or large

care provider; any subsequent management should be Managing CIN 2 or 3 in Women


according to the cytology result. If the patient requires 25 Years Old and Over
further colposcopy and the CIN lesion persists for 24 Pathologically confirmed high-grade dysplasia includes
months or longer, treatment is acceptable. If colposcopy CIN 2 and CIN 3, which are treated in the same fashion
is satisfactory, treatment may be by ablative modalities. in most jurisdictions.7,58-62 There are, however, differences
However in an adherent patient, longer follow-up is in the rates of regression. The seminal review by Ostor
possible, especially in women who have not completed showed that CIN 2 regressed in 43% of cases and
childbearing. progressed to CIN 3+ in 27%.52 This compares with
regression of 33%, persistence of 52%, and progression
The exception to a conservative approach occurs when a to invasion in at least 12% of CIN 3 cases57 (Table 2). The
diagnosis of CIN 1 is preceded by HSIL or AGC cytology. true malignant potential of CIN 3 has been demonstrated
In these situations, histological findings have not adequately in New Zealand by long-term follow-up of CIN 3 that was
explained the abnormal cytology. If specimens are available not treated. This showed that the invasive risk in untreated
the cytology and histology should be reviewed and if the CIN 3 is 31% over 30 years. The study also noted that
discrepancy is confirmed an excisional procedure may be patients with documented persistent CIN 3 for 2 years had
considered. a 50% risk of subsequently developing invasive disease.63
Recommendations For these reasons, most women with CIN 2 or 3 should be
27. The preferred option for biopsy-proven CIN 1 is treated. Women who are younger or pregnant are managed
observation with repeat assessment at 12 months as outlined elsewhere in this document. If colposcopy is
with cytology testing. (Colposcopy at 12 months satisfactory, i.e., a type 1 or 2 TZ, excision and ablative therapy
is an acceptable option.) Management should be are both acceptable; however, an excisional procedure
according to the cytology result. (II-1B) is preferred for the treatment of CIN 3. If CIN 2 or 3 is
28. In the case of a patient with biopsy-proven CIN 1 identified and colposcopy is unsatisfactory, an excisional
after HSIL or AGC, cytology and histology should procedure should be performed. Women are at increased risk
be reviewed, where available. If a discrepancy of persistent dysplasia if at treatment margins are positive
remains, then an excisional biopsy may be for CIN, or the ECC (if done) is positive. In a meta-analysis
considered. (III-B) of excisional treatment, the risk of post-treatment disease

1196 l DECEMBER JOGC DCEMBRE 2012


Colposcopic Management of Abnormal Cervical Cytology and Histology

was 18% for incomplete excision and 3% for complete 33. CIN 3 in women less than 25 years old should be
excision.64 If the deep margins are involved, consideration treated. (III-B)
should be given to repeat excision. Most women should
have colposcopy repeated at 6 months.65 Hysterectomy is Managing Adenocarcinoma in Situ
not recommended as initial therapy for CIN 2 or 3 but may In Canada the ratio of adenocarcinoma to squamous
be performed for women with persistent CIN. carcinoma of the cervix is increasing: adenocarcinoma
accounts for 20% to 25% of all cervical cancer.68 This is
Recommendations
largely because widespread availability of screening by Pap
29. CIN 2 or 3 should be treated. Excisional smears over several decades has led to a significant decrease
procedures are preferred for CIN 3. (II-1A) in squamous cell cancers. Nevertheless, implementation of
30. Women who have positive margins should have cytology quality assurance initiatives in recent years has been
follow-up with colposcopy and directed biopsies associated with a decrease in adenocarcinoma of the cervix.
and/or endocervical curettage. Treatment for
recurrent or persistent CIN 2 or 3 should be by In contrast, diagnosis of premalignant adenocarcinoma in
excision. (II-1B) situ occurs at a ratio of 1:50 when compared with severe
squamous dysplasia.69 Consequently a colposcopist will not
Managing CIN 2 or 3 in Women often see AIS, and the treatment remains controversial.
Less Than 25 Years Old Colposcopic features can be difficult to identify, and lesions
As discussed earlier there is little evidence to justify often extend high into the canal.70 Bertrand and colleagues
routine screening in the adolescent patient. If, however, showed that in 78% of cases the highest lesion in the canal
Pap screening is completed, these patients may be referred was less than 20mm from the exocervix and none were
for colposcopy. Management must be modified to prevent higher than 29.9mm.71 After a diagnosis of adenocarcinoma
harm. Recent evidence suggests that regression of CIN 2 in situ, made by punch biopsy or endocervical curettage, a
in this population occurs at a rate similar to CIN 1.10,40,66,67 diagnostic excisional procedure, or type 3 TZ excision should
The evidence suggests that CIN 2 in the adolescent can be performed. Margin status is an important predictor of
be observed with repeat colposcopy and cytology every residual disease, and thus the method chosen for treatment
6 months for up to 24 months. If dysplasia persists, the must preserve the ability to assess the endocervical margin.
patient should be treated, with either ablative methods or A recent meta-analysis of 33 studies showed that the risk of
LEEP. This is conditional on a satisfactory colposcopy. residual disease was 2.6% with negative margins and 19.4%
If colposcopy is unsatisfactory, treatment should consist with positive margins. Invasive carcinoma was also more
of an excisional procedure. A recent study of regression frequently associated with positive margins (5.2%) than with
rates of CIN 2 in women less than 25 years old (most negative margins (0.1%).72 Thus, if margins are positive, a
of whom were 20 to 25 years old) found that the overall second excision is required.
regression rate over a median of 8 months was 62%. This If AIS is diagnosed after a LEEP procedure is completed
suggests that observation may be reasonable in women (because of a CIN finding), the margins need to be carefully
less than 25 years old.18 In some centres, high-grade examined. If the AIS is small and margins are clear, there
histology is designated as HSIL, i.e., CIN terminology is no need to perform an excisional procedure unless
is not used. If the biopsy specimen is reported as HSIL childbearing is complete, when hysterectomy should be
in an adolescent woman we recommend a review of the considered.73 If fertility is not an issue or negative margins
histology using CIN terminology as suggested by the cannot be achieved, a hysterectomy is recommended.72
College of American Pathologists/American Society
of Colposcopy and Cervical Pathology consensus. After treatment for AIS, if the woman wishes to preserve
If specimen is reclassified as CIN 3, treatment by an her fertility, she can be closely observed in the colposcopy
excisional method is preferred. clinic. She should be seen for colposcopy, ECC, and
cytology testing every 6 to 12 months, for at least 5 years.
Recommendations
HR-HPV testing can be used to reassure the patient.
31. The pathologist should be asked to clarify whether Thereafter the patient should have annual cytology testing.
the lesion is CIN 2 or CIN 3. (III-B)
32. CIN 2 in women less than 25 years old should be Recommendations
observed with colposcopy at 6-month intervals 34. If AIS is diagnosed, treatment needs to be
for up to 24 months before treatment is a diagnostic excisional procedure, or type 3
considered. (II-2B) transformation zone excision. (II-2A)

DECEMBER JOGC DCEMBRE 2012 l 1197


SOGC joint clinical practice guideline

35. If margins are positive after diagnostic excisional Recommendations


procedure, a second excisional procedure should Either option is acceptable:
be performed. (II-2A) 39. Women should be followed with cytology testing
36. If after treatment for AIS a woman has and colposcopy at 6-month intervals for 2 visits.
finished childbearing, a hysterectomy should If both cytology and any biopsies are negative,
be considered. (III-B) they will then return to screening per provincial/
37. If AIS is diagnosed after LEEP is performed territorial guidelines. (II-2B)
for CIN in a woman who has not completed 40. HPV testing at 6 months combined with cytology
her family and margins are negative, it is testing is acceptable. If both are negative, women
unnecessary to perform a further diagnostic may return to screening per provincial/territorial
excisional procedure. (II-2E) guidelines. (II-2B)
Managing Histological Abnormalities Managing Histological Abnormalities
During Pregnancy in Women at High Risk
The aim of colposcopy in pregnancy is to rule out a diagnosis Numerous medical conditions and the medications used to
of invasive or micro-invasive carcinoma. If invasive or treat them reportedly affect the ability to limit progression
micro-invasive carcinoma is diagnosed, these cases should of HPV infection to dysplasia, and hence are associated with
be promptly referred to a gynaecologic oncologist. If CIN dysplasia. These include transplantation with associated
2 or CIN 3 is diagnosed during pregnancy, the available immunosuppression and medication for conditions such
evidence would suggest that treatment can be delayed until as Crohns disease, rheumatoid arthritis, diabetes, or HIV
after delivery. The risk of progression is not affected by the infection, although most available information relates to
pregnancy, and the rate of regression to CIN 1 or normal transplant and HIV patients. In a review from 1995, 144
post pregnancy is between 31% and 47%.74,75 women were followed after renal transplant. There was
a 17.5% incidence of dysplasia.86 Similar outcomes were
Recommendation
reported after liver transplant, as well as a 13% incidence
38. If CIN 2 or CIN 3 is suspected or diagnosed of HSIL.87
during pregnancy, repeat colposcopy and
treatment should be delayed until 8 to 12 weeks The link between cervical cancer and HIV is well
after delivery. (II-2A) documented. The rate of cervical cancer is up to 4 to 6
times higher in HIV-positive women.88 In recent years
Follow-up Post Treatment improved survival has been attributed to the availability
Once treated for CIN or AIS, a woman remains at risk of of highly active antiretroviral therapy.88 A review of 400
persistence or recurrence and at long-term risk of invasive women who were HIV-positive found that HR-HPV
carcinoma.62,76,77 Failure rates following treatment for CIN was present in 68% of these women and that 55% had
do not vary significantly with the treatment method used, abnormal Pap smears. Most Pap smear results were low-
and in published series are between 5% and 13%.78,79 grade changes, of which only 4% progressed and 13%
The aim of follow-up is to detect persistent or recurrent were HSIL.89 In one review from North America the rates
dysplasia. of CIN 2+ with an ASC US/LSIL referral were 13.3% in
HIV-negative women and 15.3% in HIV-positive women.90
Conventionally in Canada, women are followed after
treatment with colposcopy and cytology testing at 6-month There is no good evidence to recommend routine
intervals for 1 to 2 years, and then return to having annual colposcopy in this group, and they can be screened with
cytology testing with their primary health care provider. In annual Pap smears.91 Women in whom CIN 1 is diagnosed
recent years the availability of HR-HPV testing has raised at colposcopy can be observed and treated for persistent
the possibility of its use as follow-up with women who disease. CIN 2 and CIN 3 need to be treated, and excisional
have tested positive and potentially to detect recurrence methods are preferred. Because there is a high rate of
or persistence earlier. Reviews and meta-analyses have recurrence, a wide excision should be used.92 Highly active
evaluated this approach and demonstrated that HPV testing antiretroviral therapy seems to decrease recurrence.
may be more sensitive for detecting recurrence.22,8083 It
Recommendation
has been noted that an adequately powered prospective
trial is needed to truly evaluate this issue.83,84 Such a trial is 41. Immunocompromised women do not require
underway in several Canadian centres.85 screening colposcopy. (II-2D)

1198 l DECEMBER JOGC DCEMBRE 2012


Colposcopic Management of Abnormal Cervical Cytology and Histology

WAIT TIMES FOR COLPOSCOPY 5. Australian National Health and Medical Research Council. Screening to
prevent cervical cancer: guidelines for the management of asymptomatic
Patients with abnormal screening tests should be seen for women with screen detected abnormalities. 2005. Available at:
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